CD4 T cells control development and maintenance of brain-resident CD8 T cells during polyomavirus infection

Taryn E. Mockus, Shwetank, Matthew D. Lauver, Heather M. Ren, Colleen S. Netherby, Tarik Salameh, Yuka Imamura Kawasawa, Feng Yue, James R. Broach, Aron E. Lukacher*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Tissue-resident memory CD8 T (T RM ) cells defend against microbial reinfections at mucosal barriers; determinants driving durable T RM cell responses in non-mucosal tissues, which often harbor opportunistic persistent pathogens, are unknown. JC polyomavirus (JCPyV) is a ubiquitous constituent of the human virome. With altered immunological status, JCPyV can cause the oft-fatal brain demyelinating disease progressive multifocal leukoencephalopathy (PML). JCPyV is a human-only pathogen. Using the mouse polyomavirus (MuPyV) encephalitis model, we demonstrate that CD4 T cells regulate development of functional antiviral brain-resident CD8 T cells (bT RM ) and renders their maintenance refractory to systemic CD8 T cell depletion. Acquired CD4 T cell deficiency, modeled by delaying systemic CD4 T cell depletion until MuPyV-specific CD8 T cells have infiltrated the brain, impacted the stability of CD8 bT RM , impaired their effector response to reinfection, and rendered their maintenance dependent on circulating CD8 T cells. This dependence of CD8 bT RM differentiation on CD4 T cells was found to extend to encephalitis caused by vesicular stomatitis virus. Together, these findings reveal an intimate association between CD4 T cells and homeostasis of functional bT RM to CNS viral infection.

Original languageEnglish (US)
Article numbere1007365
JournalPLoS pathogens
Volume14
Issue number10
DOIs
StatePublished - Oct 2018

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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    Mockus, T. E., Shwetank, Lauver, M. D., Ren, H. M., Netherby, C. S., Salameh, T., Kawasawa, Y. I., Yue, F., Broach, J. R., & Lukacher, A. E. (2018). CD4 T cells control development and maintenance of brain-resident CD8 T cells during polyomavirus infection. PLoS pathogens, 14(10), [e1007365]. https://doi.org/10.1371/journal.ppat.1007365